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1.
J Law Biosci ; 11(1): lsad032, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38259629

RESUMEN

As we approach an era of potentially widespread consumer neurotechnology, scholars and organizations worldwide have started to raise concerns about the data privacy issues these devices will present. Notably absent in these discussions is empirical evidence about how the public perceives that same information. This article presents the results of a nationwide survey on public perceptions of brain data, to inform discussions of law and policy regarding brain data governance. The survey reveals that the public may perceive certain brain data as less sensitive than other 'private' information, like social security numbers, but more sensitive than some 'public' information, like media preferences. The findings also reveal that not all inferences about mental experiences may be perceived as equally sensitive, and perhaps not all data should be treated alike in ethical and policy discussions. An enhanced understanding of public perceptions of brain data could advance the development of ethical and legal norms concerning consumer neurotechnology.

2.
J Community Health ; 49(2): 314-323, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37932629

RESUMEN

BACKGROUND AND OBJECTIVE: Older persons with low socioeconomic status in the United States have different and unique health needs compared to younger persons. As part of a student-led, interprofessional partnership, we performed a needs assessment of community dwelling older persons with low socioeconomic status in an urban location within Ohio, USA. METHODS: Three entities participated in the needs assessment: a student-run health clinic, a Federally Qualified Health Center, and an apartment complex of the study population. Health professional students from medical, dental, nursing, social work, nutrition, and physician assistant programs led the needs assessment process. The process consisted of multiple phases, which included preliminary literature review, survey development, data collection, and analysis. The final survey was multidisciplinary, with six content areas covered in 37 items. RESULTS: One hundred nineteen survey responses were received, and multiple areas of need were identified including food insecurity, dental care access, and mental health. 93% of participants had at least one unmet health need and 39% of respondents met our classification for high need. The needs of the local study population had key differences from previously published data in more generalized populations of older community-dwelling individuals in the United States, notably lower utilization of dental care (43% vs. 66%), increased prevalence of possible food insecurity (30% vs. 17%), and increased use of age-appropriate preventive cancer screening services. CONCLUSIONS: Multiple areas of need were successfully identified through a student-led interprofessional needs assessment. Future student teams can address the identified needs, again through interprofessional collaborations. This process may have unique benefits to help build robust community-academic partnerships, while fostering interprofessional collaborative opportunities among healthcare students.


Asunto(s)
Relaciones Interprofesionales , Estudiantes , Humanos , Anciano , Anciano de 80 o más Años , Evaluación de Necesidades , Ohio , Atención a la Salud
3.
Vaccine ; 41(47): 6980-6990, 2023 11 13.
Artículo en Inglés | MEDLINE | ID: mdl-37852870

RESUMEN

There is still a need for a better and affordable seasonal influenza vaccine and the use of an adjuvant could solve both issues. Therefore, immunogenicity of a combination of low dose of 1/5TH (3 µg of HA) a licensed seasonal flu vaccine with the novel carbohydrate fatty acid monosulfate ester (CMS)-based adjuvant was investigated in ferrets and safety in rabbits. Without CMS, hemagglutination inhibition (HI) antibody titers ranged from ≤5 to 26 three weeks post immunization 1 (PV-1) and from 7 to 134 post-immunization 2 (PV-2) in ferrets. Virus neutralizing (VN) antibody titers ranged from 20 to 37 PV-1 and from 21 to 148 PV-2. CMS caused 10 to 111- fold increase in HI titers and 3 to 58- fold increase in VN titers PV-1 and PV-2, depending on influenza strain and dose of adjuvant. Eight mg of CMS generated significantly higher antibody titers than 1 or 4 mg, while 1 and 4 mg induced similar responses. Three µg of HA plus 4 mg of CMS was considered the highest human dose and safety of two-fold this dose was determined in acute and repeated-dose toxicity studies in rabbits conducted according to OECD GLP guidelines. The test item did not elicit any clinical signs, local reactions, effect on body weight, effect on urine parameters, effect on blood biochemistry, or gross pathological changes. In blood, increased numbers of neutrophils, lymphocytes and/or monocytes were noted and in iliac lymph nodes, increased cellularity of macrophages of minimal to mild degree were observed. In both ferrets and rabbits, body temperature increased with increasing dose of CMS to a maximum of 1 ˚C during the first day post-immunization, which returned to normal values during the second day. In the local tolerance study, histopathology of the site of injection at 7 days PV-1 revealed minimal, mild or moderate inflammation in 5, 8 and 5 animals, respectively. In the repeated-dose study and 21 days PV-3, minimal, mild or moderate inflammation was observed in 15, 18 and 3 animals, respectively. We concluded that the data show CMS is a potent and safe adjuvant ready for further clinical development of a seasonal influenza vaccine and combines high immunogenicity with possible antigen-sparing capacity.


Asunto(s)
Vacunas contra la Influenza , Gripe Humana , Animales , Humanos , Conejos , Hurones , Estaciones del Año , Anticuerpos Antivirales , Gripe Humana/prevención & control , Adyuvantes Inmunológicos , Pruebas de Inhibición de Hemaglutinación , Carbohidratos , Ácidos Grasos , Anticuerpos Bloqueadores , Ésteres , Inflamación
5.
J AAPOS ; 27(2): 89.e1-89.e4, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36849036

RESUMEN

BACKGROUND: Intracranial arachnoid cysts are relatively common in the pediatric population. Rarely, they rupture, leading to acute subdural fluid collections, which can cause a sudden increase in intracranial pressure. The purpose of this study was to characterize ophthalmic sequelae in a large cohort of these patients. METHODS: The medical records of all children treated for ruptured arachnoid cysts who presented at a single tertiary pediatric hospital for initial assessment between 2009 and 2021 were reviewed retrospectively. RESULTS: Of 35 children treated for ruptured arachnoid cysts during the study period, 30 received ophthalmological examination. Papilledema was found in 57% of these children, abducens palsy in 20%, and retinal hemorrhages in 10%. Of the 30 children, 22 were seen in outpatient follow-up, of whom 5 had a best-corrected visual acuity of 20/40 or worse in one or both eyes at most recent follow-up. Cranial nerve palsies resolved in all cases without strabismus surgery. CONCLUSIONS: Given high rates of papilledema, cranial nerve palsies, and vision loss, all children with ruptured arachnoid cysts should be evaluated by pediatric ophthalmologists.


Asunto(s)
Quistes Aracnoideos , Papiledema , Niño , Humanos , Quistes Aracnoideos/complicaciones , Quistes Aracnoideos/diagnóstico , Quistes Aracnoideos/cirugía , Papiledema/diagnóstico , Papiledema/etiología , Estudios Retrospectivos , Trastornos de la Visión , Rotura/complicaciones
6.
Breast J ; 2023: 9993852, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38162957

RESUMEN

Introduction: Elucent Medical has introduced a novel EnVisio™ Surgical Navigation system which uses SmartClips™ that generate a unique electromagnetic signal triangulated in 3 dimensions for real-time navigation. The purpose of this study was to evaluate the efficacy and feasibility of the EnVisio Surgical Navigation system in localizing and excising nonpalpable lesions in breast and axillary surgery. Methods: This pilot study prospectively examined patients undergoing breast and nodal localization using the EnVisio Surgical Navigation system. SmartClips were placed by designated radiologists using ultrasound (US) or mammographic (MMG) guidance. The technical evaluation focused on successful deployment and subsequent excision of all localized lesions including SmartClips and biopsy clips. Results: Eleven patients underwent localization using 27 SmartClips which included bracketed multifocal disease (n = 4) and clipped lymph node (n = 1). The bracketed cases were each localized with 2 SmartClips. Mammography and ultrasound were used (n = 8 and n = 19, respectively) to place the SmartClips. All 27 devices were successfully deployed within 5 mm of the targeted lesion or biopsy clip. All SmartClip devices were identified and retrieved intraoperatively. No patients required a second operation for margin excision. Conclusion: In a limited sample, the EnVisio Surgical Navigation system was a reliable technology for the localization of breast and axillary lesions planned for surgical excision. Further comparative studies are required to evaluate its efficacy in relation to the other existing localization modalities.


Asunto(s)
Neoplasias de la Mama , Sistemas de Navegación Quirúrgica , Humanos , Femenino , Proyectos Piloto , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Ganglios Linfáticos/patología , Escisión del Ganglio Linfático/métodos , Biopsia del Ganglio Linfático Centinela , Axila/diagnóstico por imagen , Axila/cirugía
7.
Cochrane Database Syst Rev ; 10: CD013818, 2022 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-36239193

RESUMEN

BACKGROUND: Uveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA) and a potentially sight-threatening condition characterized by intraocular inflammation. Current treatment for JIA-associated uveitis (JIA-U) is largely based on physician experience, observational evidence and consensus guidelines, resulting in considerable variations in practice.  OBJECTIVES: To evaluate the effectiveness and safety of tumor necrosis factor (TNF) inhibitors used for treatment of JIA-U. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We last searched the electronic databases on 3 February 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing TNF inhibitors with placebo in participants with a diagnosis of JIA and uveitis who were aged 2 to 18 years old. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and graded the certainty of the body of evidence for seven outcomes using the GRADE classification. MAIN RESULTS: We included three RCTs with 134 participants. One study conducted in the USA randomized participants to etanercept or placebo (N = 12). Two studies, one conducted in the UK (N = 90) and one in France (N = 32), randomized participants to adalimumab or placebo. All studies were at low risk of bias. Initial pooled estimates suggested that TNF-inhibitors may result in little to no difference on treatment success defined as 0 to trace cells on Standardization of Uveitis Nomenclature (SUN)-grading; or two-step decrease in activity based on SUN grading (estimated risk ratio (RR) 0.66; 95% confidence interval (CI) 0.21 to 2.10; 2 studies; 43 participants; low-certainty evidence) or treatment failure defined as a two-step increase in activity based on SUN grading (RR 0.31; 95% CI 0.01 to 7.15; 1 study; 31 participants; low-certainty evidence). Further analysis using the individual trial definitions of treatment response and failure suggested a positive treatment effect of TNF inhibitors; a RR of treatment success of 2.60 (95% CI 1.30 to 5.20; 3 studies; 124 participants; low-certainty evidence), and RR of treatment failure of 0.23 (95% CI 0.11 to 0.50; 3 studies; 133 participants). Almost all the evidence was on adalimumab and the evidence on etanercept was very limited.  For secondary outcomes, one study suggests that adalimumab may have little to no effect on risk of recurrence after induction of remission at three months (RR 2.50, 95% CI 0.31 to 20.45; 90 participants; very low-certainty evidence) and visual acuity, but the evidence is very uncertain; mean difference in longitudinal logMAR score change over six months was -0.01 (95% CI -0.06 to 0.03) and -0.02 (95% CI -0.07 to 0.03) using the best and worst logMAR measurement, respectively (low-certainty evidence). Low-certainty evidence from one study suggested that adalimumab treatment results in reduction of topical steroid doses at six months (hazard ratio 3.58; 95% CI 1.24 to 10.32; 74 participants who took one or more topical steroid per day at baseline). Adverse events, including injection site reactions and infections, were more common in the TNF inhibitor group. Serious adverse events were uncommon. AUTHORS' CONCLUSIONS: Adalimumab appears to increase the likelihood of treatment success and decrease the likelihood of treatment failure when compared with placebo. The evidence was less conclusive about a positive treatment effect with etanercept. Adverse events from JIA-U trials are in keeping with the known side effect profile of TNF inhibitors. Standard validated JIA-U outcome measures are required to homogenize assessment and to allow for comparison and analysis of multiple datasets.


Asunto(s)
Artritis Juvenil , Uveítis , Adalimumab/efectos adversos , Adolescente , Artritis Juvenil/complicaciones , Artritis Juvenil/tratamiento farmacológico , Niño , Preescolar , Etanercept/efectos adversos , Humanos , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Factor de Necrosis Tumoral alfa , Uveítis/tratamiento farmacológico , Uveítis/etiología
8.
STAR Protoc ; 3(3): 101634, 2022 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-36035795

RESUMEN

Hypoxia plays a pivotal role in the pathogenesis of major causes of mortality such as cerebral ischemia. Here, we present a standardized protocol for the induction of global hypoxia and reoxygenation in Drosophila melanogaster, with details on subsequent analysis of mortality, neurobehavioral impairments, and molecular mechanisms. This protocol emphasizes the importance of controlling and monitoring specific environmental parameters to ensure reproducible results. It also highlights profound differences that can arise from variations in the age and genotype of the flies. For complete details on the use and execution of this protocol, please refer to Habib et al. (2021).


Asunto(s)
Drosophila melanogaster , Oxígeno , Animales , Hipoxia
9.
Ophthalmol Ther ; 11(2): 811-820, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35179713

RESUMEN

INTRODUCTION: Subtenon triamcinolone acetonide (Kenalog®; Bristol Myers Squibb) (STA) injections are commonly used in the treatment of adults in an outpatient setting. However, publications on detailing its outpatient use, safety, and efficacy in the pediatric population are scarce. METHODS: We reviewed STA injections performed in children in the outpatient clinics at two tertiary centers from 2014 to 2020. All children were aged ≤ 18 years and had a diagnosis of non-infectious uveitis. STA injections were done using 0.5 cc (20 mg) triamcinolone injected superotemporally with only topical anesthesia. Data on the efficacy and safety of STA in treating inflammation and compiled data on visual acuity improvement and incidence of ocular complications were evaluated. RESULTS: Forty-eight eyes in 30 patients were included. The mean age of patients was 13.1 (range 7-18) years. There were no immediate complications observed in all injections performed. At the 3-month follow-up, inflammation had improved in 85.4% of eyes, macular edema had resolved in 77.8% of eyes, and there was significant vision improvement after STA. At 6 months after STA, the incidence of ocular hypertension was 12.5% and no new cataracts had developed. CONCLUSION: STA injection with topical anesthesia was a well-tolerated, reasonable alternative for short-term treatment of uveitis among this pediatric population.

10.
Transl Stroke Res ; 13(3): 462-482, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34628598

RESUMEN

Inflammasomes are known to contribute to brain damage after acute ischemic stroke (AIS). TAK1 is predominantly expressed in microglial cells and can regulate the NLRP3 inflammasome, but its impact on other inflammasomes including NLRC4 and AIM2 after AIS remains elusive. EPO has been shown to reduce NLRP3 protein levels in different disease models. Whether EPO-mediated neuroprotection after AIS is conveyed via an EPO/TAK1/inflammasome axis in microglia remains to be clarified. Subjecting mice deficient for TAK1 in microglia/macrophages (Mi/MΦ) to AIS revealed a significant reduction in infarct sizes and neurological impairments compared to the corresponding controls. Post-ischemic increased activation of TAK1, NLRP3, NLRC4, and AIM2 inflammasomes including their associated downstream cascades were markedly reduced upon deletion of Mi/MΦ TAK1. EPO administration improved clinical outcomes and dampened stroke-induced activation of TAK1 and inflammasome cascades, which was not evident after the deletion of Mi/MΦ TAK1. Pharmacological inhibition of NLRP3 in microglial BV-2 cells did not influence post-OGD IL-1ß levels, but increased NLRC4 and AIM2 protein levels, suggesting compensatory activities among inflammasomes. Overall, we provide evidence that Mi/MΦ TAK1 regulates the expression and activation of the NLRP3, NLRC4, AIM2 inflammasomes. Furthermore, EPO mitigated stroke-induced activation of TAK1 and inflammasomes, indicating that EPO conveyed neuroprotection might be mediated via an EPO/TAK1/inflammasome axis.


Asunto(s)
Eritropoyetina , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas de Unión al Calcio/metabolismo , Proteínas de Unión al ADN/metabolismo , Eritropoyetina/metabolismo , Inflamasomas/metabolismo , Interleucina-1beta/metabolismo , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Quinasas Quinasa Quinasa PAM/metabolismo , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Microglía/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Accidente Cerebrovascular/metabolismo
12.
Int J Mol Sci ; 22(21)2021 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-34769067

RESUMEN

Hypoxia is known to impair mitochondrial and endoplasmic reticulum (ER) homeostasis. Post-hypoxic perturbations of the ER proteostasis result in the accumulation of misfolded/unfolded proteins leading to the activation of the Unfolded Protein Response (UPR). Mitochondrial chaperone TNF receptor-associated protein 1 (TRAP1) is reported to preserve mitochondrial membrane potential and to impede reactive oxygen species (ROS) production thereby protecting cells from ER stress as well as oxidative stress. The first-line antidiabetic drug Metformin has been attributed a neuroprotective role after hypoxia. Interestingly, Metformin has been reported to rescue mitochondrial deficits in fibroblasts derived from a patient carrying a homozygous TRAP1 loss-of-function mutation. We sought to investigate a putative link between Metformin, TRAP1, and the UPR after hypoxia. We assessed post-hypoxic/reperfusion longevity, mortality, negative geotaxis, ROS production, metabolic activity, gene expression of antioxidant proteins, and activation of the UPR in Trap1-deficient flies. Following hypoxia, Trap1 deficiency caused higher mortality and greater impairments in negative geotaxis compared to controls. Similarly, post-hypoxic production of ROS and UPR activation was significantly higher in Trap1-deficient compared to control flies. Metformin counteracted the deleterious effects of hypoxia in Trap1-deficient flies but had no protective effect in wild-type flies. We provide evidence that TRAP1 is crucially involved in the post-hypoxic regulation of mitochondrial/ER stress and the activation of the UPR. Metformin appears to rescue Trap1-deficiency after hypoxia mitigating ROS production and downregulating the pro-apoptotic PERK (protein kinase R-like ER kinase) arm of the UPR.


Asunto(s)
Proteínas de Drosophila/genética , Drosophila melanogaster/efectos de los fármacos , Proteínas HSP90 de Choque Térmico/genética , Hipoglucemiantes/farmacología , Metformina/farmacología , Estrés Oxidativo/efectos de los fármacos , eIF-2 Quinasa/metabolismo , Animales , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Eliminación de Gen , Proteínas HSP90 de Choque Térmico/metabolismo , Hipoxia/genética , Hipoxia/metabolismo , Masculino , Respuesta de Proteína Desplegada/efectos de los fármacos
13.
Elife ; 102021 10 29.
Artículo en Inglés | MEDLINE | ID: mdl-34711304

RESUMEN

The controllability of our social environment has a profound impact on our behavior and mental health. Nevertheless, neurocomputational mechanisms underlying social controllability remain elusive. Here, 48 participants performed a task where their current choices either did (Controllable), or did not (Uncontrollable), influence partners' future proposals. Computational modeling revealed that people engaged a mental model of forward thinking (FT; i.e., calculating the downstream effects of current actions) to estimate social controllability in both Controllable and Uncontrollable conditions. A large-scale online replication study (n=1342) supported this finding. Using functional magnetic resonance imaging (n=48), we further demonstrated that the ventromedial prefrontal cortex (vmPFC) computed the projected total values of current actions during forward planning, supporting the neural realization of the forward-thinking model. These findings demonstrate that humans use vmPFC-dependent FT to estimate and exploit social controllability, expanding the role of this neurocomputational mechanism beyond spatial and cognitive contexts.


Asunto(s)
Corteza Prefrontal/fisiología , Interacción Social , Pensamiento/fisiología , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Texas , Adulto Joven
14.
Imaging Sci Dent ; 51(3): 307-311, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34621658

RESUMEN

PURPOSE: An oroantral communication (OAC) is an abnormal space between the maxillary sinus and oral cavity. The causes, complications, treatment, and radiographic features of OAC in 2-dimensional and 3-dimensional imaging modalities are discussed. MATERIALS AND METHODS: This pictorial review presents a broad spectrum of imaging findings of OAC. Representative radiographs depicting OAC were chosen from our database. PubMed was used to conduct a comprehensive literature search of OAC. RESULTS: Characteristic features of OAC include discontinuity of the maxillary sinus floor, thickening of the maxillary sinus mucosa, or a combination of both. Two-dimensional imaging modalities are the method of choice for identifying discontinuities in the maxillary sinus floor. However, 3-dimensional imaging modalities are also essential for determining the status of soft tissue in the maxillary sinus. CONCLUSION: The integration of 2-dimensional and 3-dimensional imaging modalities is crucial for the correct diagnosis and comprehensive treatment of OAC. However, the diagnosis of OAC must be confirmed clinically to prevent unnecessary mental and financial burdens to patients.

15.
J Pediatr Ophthalmol Strabismus ; 58(3): 174-179, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34039156

RESUMEN

PURPOSE: To determine changes in the clinical treatment of pediatric patients taking vigabatrin for seizure control in response to results of electroretinogram (ERG) performed for retinal toxicity screening. METHODS: The authors retrospectively reviewed the medical records of patients who received ERGs at Children's Hospital of Colorado from 2009 to 2012. Age, indication for ERG, ERG data, and clinical management of vigabatrin were extracted from the records. ERGs were interpreted according to LKC Technologies normative values. A physician trained in ERG analysis interpreted each ERG. RESULTS: One hundred seventy ERGs were performed during the study period, and 147 ERGs were available for analysis. Every patient received general anesthesia for the procedure. Thirty-three ERGs were performed in 29 patients specifically as screening for retinal toxicity due to vigabatrin use, and 30 were available for analysis. Within this cohort, only 2 ERGs were normal (6.6%), and 28 were abnormal (93.3%). In patients who received abnormal results, 1 patient discontinued vigabatrin in response to the screening. CONCLUSIONS: In this study cohort, clinical management generally did not change in response to an abnormal screening result. Given the need for general anesthesia in the pediatric population receiving ERG testing, and minimal change in clinical decision-making in the face of abnormal results, ERG screening for retinal toxicity due to vigabatrin in the pediatric cohort should be reconsidered. [J Pediatr Ophthalmol Strabismus. 2021;58(3):174-179.].


Asunto(s)
Anticonvulsivantes , Vigabatrin , Anticonvulsivantes/efectos adversos , Niño , Electrorretinografía , Humanos , Retina , Estudios Retrospectivos , Vigabatrin/efectos adversos
16.
Exp Mol Med ; 53(2): 264-280, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33564101

RESUMEN

Hypoxia is an underlying pathophysiological condition of a variety of devastating diseases, including acute ischemic stroke (AIS). We are faced with limited therapeutic options for AIS patients, and even after successful restoration of cerebral blood flow, the poststroke mortality is still high. More basic research is needed to explain mortality after reperfusion and to develop adjunct neuroprotective therapies. Drosophila melanogaster (D.m.) is a suitable model to analyze hypoxia; however, little is known about the impacts of hypoxia and especially of the subsequent reperfusion injury on the behavior and survival of D.m. To address this knowledge gap, we subjected two wild-type D.m. strains (Canton-S and Oregon-R) to severe hypoxia (<0.3% O2) under standardized environmental conditions in a well-constructed hypoxia chamber. During posthypoxic reperfusion (21% O2), we assessed fly activity (evoked and spontaneous) and analyzed molecular characteristics (oxidative stress marker abundance, reactive oxygen species (ROS) production, and metabolic activity) at various timepoints during reperfusion. First, we established standard conditions to induce hypoxia in D.m. to guarantee stable and reproducible experiments. Exposure to severe hypoxia under defined conditions impaired the climbing ability and reduced the overall activity of both D.m. strains. Furthermore, a majority of the flies died during the early reperfusion phase (up to 24 h). Interestingly, the flies that died early exhibited elevated activity before death compared to that of the flies that survived the entire reperfusion period. Additionally, we detected increases in ROS and stress marker (Catalase, Superoxide Dismutase and Heat Shock Protein 70) levels as well as reductions in metabolic activity in the reperfusion phase. Finally, we found that changes in environmental conditions impacted the mortality rate. In particular, decreasing the temperature during hypoxia or the reperfusion phase displayed a protective effect. In conclusion, our data suggest that reperfusion-dependent death might be associated with elevated temperatures, predeath activity, and oxidative stress.


Asunto(s)
Conducta Animal , Drosophila melanogaster/metabolismo , Hipoxia/metabolismo , Estrés Oxidativo , Temperatura , Animales , Antioxidantes/metabolismo , Drosophila melanogaster/genética , Metabolismo Energético , Ambiente , Regulación de la Expresión Génica , Hipoxia/genética , Modelos Biológicos , Mortalidad , Estrés Oxidativo/genética , Especies Reactivas de Oxígeno/metabolismo , Factores de Tiempo
17.
Protein Eng Des Sel ; 332020 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-33159202

RESUMEN

Insulin is a peptide hormone produced by the pancreas. The physiological role of insulin is the regulation of glucose metabolism. Under certain pathological conditions the insulin levels can be reduced leading to the metabolic disorder diabetes mellitus (DM). For type 1 DM and, dependent on the disease progression for type 2 DM, insulin substitution becomes indispensable. To relieve insulin substitution therapy for patients, novel insulin analogs with pharmacokinetic and pharmacodynamic profiles aiming for long-lasting or fast-acting insulins have been developed. The next step in the evolution of novel insulins should be insulin analogs with a time action profile beyond 1-2 days, preferable up to 1 week. Nowadays, insulin is produced in a recombinant manner. This approach facilitates the design and production of further insulin-analogs or insulin-fusion proteins. The usage of the Fc-domain from immunoglobulin as a fusion partner for therapeutic proteins and peptides is widely used to extend their plasma half-life. Insulin consists of two chains, the A- and B-chain, which are connected by two disulfide-bridges. To produce a novel kind of Fc-fusion protein we have fused the A-chain as well as the B-chain to Fc-fragments containing either 'knob' or 'hole' mutations. The 'knob-into-hole' technique is frequently used to force heterodimerization of the Fc-domain. Using this approach, we were able to produce different variants of two-chain-insulin-Fc-protein (tcI-Fc-protein) variants. The tcI-Fc-fusion variants retained activity as shown in in vitro assays. Finally, prolonged blood glucose lowering activity was demonstrated in normoglycemic rats. Overall, we describe here the production of novel insulin-Fc-fusion proteins with prolonged times of action.


Asunto(s)
Glucemia/metabolismo , Fragmentos Fc de Inmunoglobulinas , Insulina , Proteínas Recombinantes de Fusión , Animales , Humanos , Fragmentos Fc de Inmunoglobulinas/biosíntesis , Fragmentos Fc de Inmunoglobulinas/genética , Fragmentos Fc de Inmunoglobulinas/farmacología , Insulina/biosíntesis , Insulina/genética , Insulina/farmacología , Masculino , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/farmacología
18.
J Binocul Vis Ocul Motil ; 70(3): 89-93, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32511077

RESUMEN

BACKGROUND: The purpose of this study is to compare surgical outcomes of recession, anteriorization, and myotomy for the treatment of inferior oblique overaction (IOOA). METHODS: A retrospective chart review of all patients undergoing IOOA correction from July 2010 to March 2017 at the Children's Hospital of Colorado was performed. Preoperative grading of IOOA (+0.5 to +4.0) was compared to post-operative IOOA (0 to +4.0). The goal was reduction of IOOA to 0, but any decrease in IOOA was measured. RESULTS: There were a total of 260 patients with 357 eyes. Gender and age were similar across surgery types. A 94.6% of eyes had a decrease in IOOA with recession (n = 165) of the inferior oblique while 86.1% decreased to no IOOA. Anteriorization of the inferior oblique (n = 115) decreased overaction in 97.4% of eyes with 81.7% improving to zero degree of IOOA. Myotomy of the inferior oblique (n = 77) was found to decrease overaction in 98.7% of eyes and reduce IOOA to zero in 88.3%. There was no significant difference among type of surgery and outcome. CONCLUSION: All three surgical interventions were found to be equally successful in reducing the amount of IOOA.


Asunto(s)
Músculos Oculomotores/cirugía , Procedimientos Quirúrgicos Oftalmológicos , Estrabismo/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Movimientos Oculares/fisiología , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Miotomía , Músculos Oculomotores/fisiopatología , Periodo Posoperatorio , Estudios Retrospectivos , Estrabismo/fisiopatología , Resultado del Tratamiento , Visión Binocular/fisiología
19.
Cornea ; 39(12): 1516-1519, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32398424

RESUMEN

PURPOSE: To describe the ocular complications experienced by patients with pontine tegmental cap dysplasia (PTCD) and the management strategies used to care for these children. METHODS: Subjects with PTCD were recruited through social media advertisement and completed a survey gathering information on potential ocular problems related to the patient's PTCD disease and any current or previous treatments. RESULTS: Twenty-two patients or guardians completed the survey. Neurotrophic cornea was the most common ocular diagnosis (82%), followed by facial palsy (59%), dry eye syndrome (59%), and blepharitis (55%). Other diagnoses included cortical visual impairment (27%), strabismus (27%), amblyopia (18%), and nystagmus (18%). Common treatment modalities included lubricating eye drops (59%) or ointment (50%), contact lenses (14%), punctal plugs (27%), glasses (45%), and patching (18%). The most common surgical interventions were temporary or permanent tarsorrhaphy (64%) and amniotic membrane grafts (23%). In total, 68% of families reported self-injury to eyes and 91% reported the child to be primarily a visual learner. CONCLUSIONS: PTCD is a newly described, very rare disorder with a variety of vision-threatening ocular manifestations. It is essential that the ophthalmologist be aware of the potential for neurotrophic cornea because timely treatment could prevent corneal scarring, perforation, and blindness.


Asunto(s)
Enfermedades Cerebelosas/diagnóstico , Enfermedades de los Nervios Craneales/diagnóstico , Discapacidades del Desarrollo/diagnóstico , Oftalmopatías/diagnóstico , Malformaciones del Sistema Nervioso/diagnóstico , Tegmento Pontino/anomalías , Adolescente , Enfermedades Cerebelosas/etiología , Preescolar , Enfermedades de los Nervios Craneales/etiología , Discapacidades del Desarrollo/etiología , Oftalmopatías/etiología , Femenino , Humanos , Masculino , Malformaciones del Sistema Nervioso/etiología
20.
Immunohematology ; 36(1): 1-3, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32324037

RESUMEN

CONCLUSIONS: The presence of HLA antibodies in patient serum or plasma may make antibody identification difficult. These HLA antibodies may mask the presence of clinically significant red blood cell (RBC) alloantibodies. Because platelets strongly express HLA antigens, it is possible to remove HLA antibodies by adsorbing the patient's serum or plasma using a platelet pool. Large numbers of random platelets are pooled to ensure a wide variety of HLA types are present. Elimination of the reactivity after adsorption suggests the presence of HLA antibodies in the patient's serum or plasma. The adsorbed patient sample may then be used to evaluate RBC alloantibodies without HLA antibody interference.


Asunto(s)
Plaquetas , Adsorción , Eritrocitos , Antígenos HLA , Humanos , Isoanticuerpos
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